Reducing persistent polyomavirus infection increases functionality of virus-specific memory CD8 T cells

•Construction of a recombinant mouse polyomavirus (MuPyV) carrying two loxP sites.•Cre recombinase expression reduces acute and persistent infection levels of MuPyV-loxP.•Expansion of virus-specific CD8 T cells is blunted with Cre induction in acutely infected mice.•Cre induction in persistently infected mice improves memory CD8 T cell recall responses.

Mouse polyomavirus (MuPyV) causes a smoldering persistent infection in immunocompetent mice. To lower MuPyV infection in acutely and persistently infected mice, and study the impact of a temporal reduction in viral loads on the memory CD8 T cell response, we created a recombinant MuPyV in which a loxP sequence was inserted into the A2 strain genome upstream of the early promoter and another loxP sequence was inserted in cis into the intron shared by all three T antigens. Using mice transgenic for tamoxifen-inducible Cre recombinase, we demonstrated that reduction in MuPyV load during persistent infection was associated with differentiation of virus-specific CD8 T cells having a superior recall response. Evidence presented here supports the concept that reduction in viral load during persistent infection can promote differentiation of protective virus-specific memory CD8 T cells in patients at risk for diseases caused by human polyomaviruses.